Open Access Research article

An intron polymorphism of the fibronectin gene is associated with end-stage knee osteoarthritis in a Han Chinese population: two independent case-control studies

Hsin-Yi Yang1, Sui-Lung Su1, Yi-Jen Peng2, Chih-Chien Wang34, Herng-Sheng Lee2, Donald M Salter5 and Chian-Her Lee6*

Author Affiliations

1 School of Public Health, National Defense Medical Center, Taipei, Taiwan

2 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

3 Department of Orthopedics, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan

4 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

5 Centre for Molecular Medicine, MRC IGMM, University of Edinburgh, Edinburgh, UK

6 Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University and Hospital, No.250, Wuxing St., Xinyi Dist, Taipei, Taiwan

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BMC Musculoskeletal Disorders 2014, 15:173  doi:10.1186/1471-2474-15-173

Published: 23 May 2014

Abstract

Background

Knee osteoarthritis (OA) is a complex disease involving both biomechanical and metabolic factors that alter the tissue homeostasis of articular cartilage and subchondral bone. The catabolic activities of extracellular matrix degradation products, especially fibronectin (FN), have been implicated in mediating cartilage degradation. Chondrocytes express several members of the integrin family which can serve as receptors for FN including integrins α5β1, αvβ3, and αvβ5. The purpose of this study was to determine whether polymorphisms in the FN (FN-1) and integrin genes are markers of susceptibility to, or severity of, knee OA in a Han Chinese population.

Methods

Two independent case–control studies were conducted on 928 patients with knee OA and 693 healthy controls. Ten single nucleotide polymorphisms (SNPs) of FN-1 and the integrin αV gene (ITGAV) were detected using the ABI 7500 real-time PCR system.

Results

The AT heterozygote in FN-1 (rs940739A/T) was found to be significantly associated with knee OA (adjusted OR = 1.44; 95% CI = 1.16–1.80) in both stages of the study. FN-1 rs6725958C/A and ITGAV rs10174098A/G SNPs were only associated with knee OA when both study groups were combined. Stratifying the participants by Kellgren-Lawrence (KL) score identified significant differences in the FN-1 rs6725958C/A and rs940739 A/T genotypes between patients with grade 4 OA and controls. Haplotype analyses revealed that TGA and TAA were associated with a higher risk of OA, and that TAG conferred a lower risk of knee OA in the combined population.

Conclusions

Our study suggests that the FN-1 rs940739A/T polymorphism may be an important risk factor of genetic susceptibility to knee OA in the Han Chinese population.

Keywords:
Knee osteoarthritis; Fibronectin gene; Integrin αV gene; Single nucleotide polymorphism